Cited by 53Pancreatic and Hepatic Oncology ResearchCancer Cells and Metastasis3D Printing in Biomedical Research

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Pre-clinical Models of Metastasis in Pancreatic Cancer

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Miquel, Maria, Zhang, Shuman, Pilarsky, Christian·2021·Frontiers in Cell and Developmental Biology

DOI 10.3389/fcell.2021.748631PMC PMC8578999

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a hostile solid malignancy coupled with an extremely high mortality rate. Metastatic disease is already found in most patients at the time of diagnosis, resulting in a 5-year survival rate below 5%. Improved comprehension of the mechanisms leading to metastasis is pivotal for the development of new targeted therapies. A key field to be improved are modeling strategies applied in assessing cancer progression, since traditional platforms fail in recapitulating the complexity of PDAC. Consequently, there is a compelling demand for new preclinical models that mirror tumor progression incorporating the pressure of the immune system, tumor microenvironment, as well as molecular aspects of PDAC. We suggest the incorporation of 3D organoids derived from genetically engineered mouse models or patients as promising new tools capable to transform PDAC pre-clinical modeling and access new frontiers in personalized medicine.

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FIGURE 1 Stages of Metastatic Progression with candidate genes responsible per each stage. (1) Normal epithelial pancreatic ductal cells acquire an aggressive phenotype through serial mutations that transform them firstly to PanIN and lately to PDAC. (2) Transformed cells are capable of detaching and colonizing the Peritoneum forming Ascites or Pleural Effusion. (3) PDAC cells have enhanced motility due to EMT that allows them to invade blood or lymphatic vessels. (4) CTCs in circulation are abundant, but only few survive this pressure. (5) Several CTCs have tropism for the pre-metastatic niche (PMN) and are able to extravasate to a secondary organ where they might remain dormant (6) for several years and eventually relapse and form overt metastasis (7).CC BY · PubMed Central

FIGURE 2 Overview of the current models to study metastasis in PDAC. The color scale indicates whether a model is more suitable (green) or less (red) for each purpose.CC BY · PubMed Central

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2021, PancREatic Cancer OrganoiDs rEsearch Network | PRECODE Project | H2020 | CORDIS | European Commission.

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See all 53

Authors: Miquel, M., Zhang, S., & Pilarsky, C.
Affiliations: Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Corresponding author: Pilarsky, Christian
ORCID: Zhang, Shuman
Pilarsky, Christian
Venue: Frontiers in Cell and Developmental Biology
Publisher: Frontiers Media SA
Published: 2021-10-27
Volume: 9
Pages: 748631-748631
ISSN: 2296-634X (ISSN-L)
DOI: 10.3389/fcell.2021.748631
PMC: PMC8578999
OpenAlex: W3210638807
Cited by: 53
References: 228
Citations by year: 2026: 10 · 2025: 13 · 2024: 16 · 2023: 7 · 2022: 7
FWCI: 0.91
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, other-oa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion, cc-by)
Funders: H2020 Marie Skłodowska-Curie Actions (861196)
China Sponsorship Council (201806880012)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords: pancreatic ductal adenocarcinoma, metastasis, preclinical models, 3D organoids, genetically engineered mouse models, tumor microenvironment, immune system, tumor progression, personalized medicine, targeted therapy

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